Human skin is comprised of layers. The epidermis is the outermost layer and comprises a cellular continuum of four layers: the stratum corneum, the granular layer, the spinous layer, and the basal layer. Each layer in the epidermis represents various stages along a process in which skin cells undergo a continuous cycle of proliferation, differentiation, and apoptosis.
The basal layer forms the lower portion of the epidermis and contains basal keratinocytes, mitotically active cells that undergo a proliferative cycle to generate daughter cells that are physically dislocated upward into the spinous and granulous layers above. As the cells migrate upward, they lose their central nucleus and start to produce skin proteins (keratins) and fats (lipids). On passing through the spinous and granulous layers, the cells undergo a process of differentiation into corneocytes and undergo morphological changes that flatten their structure as they lose cellular viability, alter their keratin expression profiles, and transform themselves into cellular remnants, thereby forming the stratum corneum. The corneocytes in the stratum corneum remain connected to each other via proteins and lipids, which create a protective barrier against chemical and biological insults from the outside environment. For example, the barrier attenuates the penetration of harmful radiation, including ultraviolet (UV) radiation, into deeper skin layers. The stratum corneum also acts as a permeability barrier and functions to prevent loss of body moisture to the outside environment. Dysfunction of the epidermal barrier can lead to chronic skin conditions, disease, and in extreme cases, can even threaten the viability of the organism.
Skin aging is a multifactorial process driven by both intrinsic and extrinsic factors. Intrinsic factors include chronological aging and other biochemical changes occurring in skin cells. Extrinsic factors include UV exposure, toxins, pollutants, wind, heat, low humidity, harsh surfactants, abrasives, smoke and other environmental elements. On average, a younger epidermis turns over in about one month, shedding the older cells and replacing them with new ones, but the same process can take over forty days in older skin. As skin ages, the cornified layer becomes gradually thinner, which results in a reduction in the functioning capacity of the barrier. Impairment of the barrier allows harmful stimuli to penetrate the stratum corneum more easily, leading to damage of the underlying dermal layers, degradation of the structural proteins collagen and elastin, and eventually skin wrinkling and atrophy. Additionally, the increase in permeability and a reduction in the amount of lipid in the intercellular matrix decreases the capacity of the barrier to diffuse, i.e., remove, toxins from deeper skin layers. The recovery capacity of the barrier to environmental insult is thus substantially reduced with age.
The effects of aging can result in a number of visible changes in the appearance of skin. Thinning of the stratum corneum and general degradation of the skin by intrinsic and/or extrinsic factors increases the visible appearance of fine lines, wrinkles, inflammation, uneven skin tone and other signs of skin aging. For example, in young skin, melanin is evenly distributed, but as skin ages or is exposed to damaging environmental effects, melanocytes lose their normal regulation process and produce excess pigment, leading to areas of hyperpigmentation such as age spots (lentigines) and uneven skin tone.
Topical compositions comprising vitamin B3 compounds are known to effectively regulate skin appearance, as described in U.S. Pat. No. 5,939,082. For example, topical niacinamide can regulate the signs of skin aging, e.g., reduce or efface the visibility of the fine lines, wrinkles, and uneven skin tone associated with aging skin. However, compositions and methods of treatment that are even more effective than currently marketed products at improving the health and appearance of aging skin are continuing desires in the personal care and cosmetic fields.